Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis

Hormone replacement therapy (HRT) increases the risk of venous thrombosis. We investigated whether this risk is affected by carriership of hereditary prothrombotic abnormalities. Therefore, we determined the two most common prothrombotic mutations, factor V Leiden and prothrombin 20210A in women who participated in a case-control study on venous thrombosis. Relative risks were expressed as odds ratios (OR) with 95% confidence intervals (CI95). Among 7 7 women aged 45-64 years with a first venous thrombosis, 51% were receiving HRT at the time of thrombosis, compared with 24% of control women (OR = 3.3, CI95 1.8-5.8). Among the patients, 23% had a prothrombotic defect, versus 7% among the control women (OR = 3.8, CI95 1.7- 8.5). Women who had factor V Leiden and used HRT had a 15-fold increased risk (OR = 15.5, CI95 3.1-77), which exceeded the expected joint odds ratio of 6.1 (under an additive model). We conclude that the thrombotic risk of HRT may particularly affect women with prothrombotic mutations. Efforts to avoid HRT in women with increased risk of thrombosis are advisable

The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study

Objective To assess the thrombotic risk associated with oral contraceptive use with a focus on dose of oestrogen and type of progestogen of oral contraceptives available in the Netherlands

Minimal dataset for post-registration surveillance of new drugs in hemophilia: communication from the SSC of the ISTH

Clinical epidemiolog

Reproducibility of exhaled nitric oxide measurements in overweight and obese adults

Exhaled nitric oxide is a noninvasive measure of airway inflammation that can be detected by a handheld device. Obesity may influence the reproducibility of exhaled nitric oxide measurements, by - for instance - decreased expiratory reserve volume. We analyzed triple exhaled nitric oxide measurements from 553 participants (aged 45 to 65 years with a body mass index ≥27 kg/m2) of the Netherlands Epidemiology of Obesity Study. The interclass correlation coefficient (single measurement reliability) was 0.965 (95% CI: 0.960, 0.970). We conclude that for assessment of exhaled nitric oxide in large cohorts of overweight and obese adults a single measurement suffice

HMG-CoA reductase inhibitors, other lipid-lowering medication, antiplatelet therapy, and the risk of venous thrombosis

Background: Statins [3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors] and antiplatelet therapy reduce the risk of atherosclerotic disease. Besides a reduction of lipid levels, statins might also have antithrombotic and anti-inflammatory properties, and anti-platelet therapy reduces clot formation. We have studied the risk of venous thrombosis with use of statins, other lipid-lowering medication, and antiplatelet therapy. Materials and methods: Patients with a first episode of deep vein thrombosis in the leg or pulmonary embolism between March 1999 and September 2004 were included in a large population-based case–control study (MEGA study). Control subjects were partners of patients (53%) or recruited via a random-digit-dialing method (47%). Participants reported different all-medication use in a questionnaire. Results: Of 4538 patients, 154 used statins (3.3%), as did 354 of 5914 control subjects (5.7%). The use of statins [odds ratio (OR) 0.45; 95% confidence interval (CI) 0.36–0.56] but not other lipid-lowering medications (OR 1.22; 95% CI 0.62–2.43), was associated with a reduced venous thrombosis risk as compared with individuals who did not use any lipid-lowering medication, after adjustment for age, sex, body mass index, atherosclerotic disease, antiplatelet therapy and use of vitamin K antagonists. Different types and various durations of statin therapy were all associated with a decreased venous thrombosis risk. Antiplatelet therapy also reduced venous thrombosis risk (OR 0.56; 95% CI 0.42–0.74). However, sensitivity analyses suggested that this effect is most likely explained by a so-called ‘healthy user effect’. Simultaneous use of medication most strongly reduced venous thrombosis risk. Conclusion: These results suggest that the use of various types of statins is associated with a reduced risk of venous thrombosis, whereas antiplatelet therapy and other lipid-lowering medications are not.\u

Optimal intensity of oral anticoagulant therapy after myocardial infarction

AbstractObjectives.This study attempted to determine the optimal intensity of anticoagulant therapy in patients after myocardial infarction.Background.Treatment with oral anticoagulant therapy entails a delicate balance between over- (risk of bleeding) and under-anticoagulant (risk of thromboemboli). The optimal intensity required to prevent the occurrence of either event (bleeding or thromboembolic) is not known.Methods.A method was used to determine the optimal intensity of anticoagulant therapy by calculating incidence rates for either event associated with a specific international normalized ratio. The numerator included events occurring at given international normalized ratios, and the denominator comprised the total observation time.Results.The study population included 3,404 myocardial infarction patients enrolled in the ASPECT (anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis) trial. Total treatment was 6,918 patient-years. Major bleeding occurred in 57 patients (0.8/100 patient-years), and thromboembolic complications in 397 (5.7/100 patient-years). The incidence of the combined outcome (bleeding or thromboembolic complications) with international normalized ratio < 2 was 8.0/100 patient-years (283 events in 3,559 patient-years), with international normalized ratios between 2 and 3, 3.9/100 patient-years (33 events in 838 patient-years); 3.2/100 patient-years (57 events in 1,775 patient-years) for international normalized ratios between 3 and 4; 6.6/100 patient-years (37 events in 564 patient-years) for international normalized ratios between 4 and 5; and 7.7/100 patient-years (14 events in 182 patient-years) for international normalized ratios >5. After adjustment for achieved international normalized ratio levels, significant predictors were higher levels of systolic blood pressure and age.Conclusions.If equal weight is given to hemorrhagic and thromboembolic complications, these results suggest that the optimal intensity of long-term anticoagulant therapy for myocardial infarction patients lies between 2.0 and 4.0 international normalized ratio, with a trend to suggest an optimal intensity of 3.0 to 4.0

A Precision Measurement of pp Elastic Scattering Cross Sections at Intermediate Energies

We have measured differential cross sections for \pp elastic scattering with internal fiber targets in the recirculating beam of the proton synchrotron COSY. Measurements were made continuously during acceleration for projectile kinetic energies between 0.23 and 2.59 GeV in the angular range $30 \leq \theta_{c.m.} \leq 90$ deg. Details of the apparatus and the data analysis are given and the resulting excitation functions and angular distributions presented. The precision of each data point is typically better than 4%, and a relative normalization uncertainty of only 2.5% within an excitation function has been reached. The impact on phase shift analysis as well as upper bounds on possible resonant contributions in lower partial waves are discussed.Comment: 23 pages 29 figure

Measurement of Spin Correlation Parameters ANN_{NN}, ASS_{SS}, and A_SL{SL} at 2.1 GeV in Proton-Proton Elastic Scattering

At the Cooler Synchrotron COSY/J\"ulich spin correlation parameters in elastic proton-proton (pp) scattering have been measured with a 2.11 GeV polarized proton beam and a polarized hydrogen atomic beam target. We report results for A$_{NN}$, A$_{SS}$, and A_${SL}$ for c.m. scattering angles between 30$^o$ and 90$^o$. Our data on A$_{SS}$ -- the first measurement of this observable above 800 MeV -- clearly disagrees with predictions of available of pp scattering phase shift solutions while A$_{NN}$ and A_${SL}$ are reproduced reasonably well. We show that in the direct reconstruction of the scattering amplitudes from the body of available pp elastic scattering data at 2.1 GeV the number of possible solutions is considerably reduced.Comment: 4 pages, 4 figure